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Trichinella spiralis:Quantitative relationships between intestinal worm burden, worm rejection, and the measurement of intestinal immunity in inbred mice

Authors
Journal
Experimental Parasitology
0014-4894
Publisher
Elsevier
Publication Date
Volume
66
Issue
1
Identifiers
DOI: 10.1016/0014-4894(88)90049-5
Keywords
  • Inbred Mice
  • Trichinella Spiralis
  • Dose Response
  • Intestinal Rejection
  • Immunosuppression
  • Initiation Of Rejection
  • Mathematical Analysis
Disciplines
  • Mathematics

Abstract

Abstract The effect of widely different doses of Trichinella spiralis muscle larvae on time to rejection of intestinal adults and on host survival was assessed in mice of the three rejection phenotypes; strong, intermediate, and weak. Rejection is weak with doses of less than 50 larvae per mouse. At these doses all mice rejected worms at a similar rate and no phenotypic variation was evident among strains. In contrast, rejection time was shortest for all strains and phenotypic variation among strains was evident in the range 50–100 muscle larvae/mouse. Above this dose the time taken to rejection increases monotonically with dose for all mouse strains examined. Despite this, the relative strength of rejection (i.e., phenotype) of a given strain of mouse was not changed at higher doses. Based on an end point of 98% rejection of the infective dose, time to rejection was predictable to ± 1 day for all mouse strains and doses tested over the range 100–1000 worms administered. The principal reason for the increased time to complete rejection with larger worm doses was a delay in the initiation of intestinal rejection. This delay was evident above a dose of 50–100 larvae per mouse and occurred in all strains. Once begun, rejection was faster and eliminated more worms in unit time at higher doses (400–800 more) than at lower doses of worms. This appeared to be due to a stronger immune response of the host at higher doses. However, the increase in the rate of rejection was still not as great as the increase in the dose. We postulate that the delay in rejection with increased dose is due to a requirement for a “critical mass” of effectors/worm required to cause rejection. As dose increases, more time is required to reach the level at which worm rejection commences. Deaths due to higher doses of worms also occurred in a strain specific manner and were temporally biphasic. The intestinal phase of infection produced mortality from 1 to 5 days after infection and the strongest rejection phenotype (NFS) was also the most resistant to intestinal deaths. Deaths occurring after Day 5 were due to the parenterally migrating newborn larvae. The weakest rejection phenotype, that of the B10 congenics, was also the least resistant to intestinal deaths. An experimental formula describing 98% worm rejection time with different doses was derived from the data. Simple dynamical system theory was used to explain several experimental observations relating dose to rejection time. The mathematical analysis and the experimental observations do not support selective dose-dependent immunosuppression of worm rejection.

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